Antihypertensive amides

Abstract

Compounds of the structure: <IMAGE> wherein R1, R2, R3, R4, R5, and R6 are hydrogen, alkyl, alkenyl, alkynyl, phenyl-alkyl, or cycloalkyl, n is an integer from 0 to 4 inclusive, M is alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, polycycloalkyl, polycyclo-alkyl-alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, hetero-cycloalkyl, hetero-cycloalkyl-alkyl, alkoxyalkyl, alkylthioalkyl, alkylamino-alkyl, dialkylamino-alkyl, fused aryl-cycloalkyl, fused aryl-cycloalkyl-alkyl, fused heteroaryl-cycloalkyl, or fused heteroaryl-cycloalkyl-alkyl, Y is hydroxy, alkoxy, amino, or substituted amino, aminoalkanoyl, aryloxy, aminoalkoxy, or hydroxyalkoxy, and R7 is hydrogen, alkanoyl, carboxylalkanoyl, hydroxyalkanoyl, amino-alkanoyl, cyano, amidino, carbalkoxy, ZS, or <IMAGE> wherein Z is hydrogen, alkyl, hyroxyalkyl, aminoalkyl or the radical <IMAGE> wherein R1, R2, R3, R4, R5, R6, n, M and Y are as described above; and where Y is hydroxy their non-toxic, pharmaceutically acceptable alkali metal, alkaline earth metal, and amine salts.

We claim: 
     
       1. Compounds of the structure ##STR13## wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are independently hydrogen, lower alkyl, lower alkenyl, lower alkenyl, or phenyl-lower alkyl, wherein the lower alkyl, lower alkenyl and lower alkynyl groups have up to 6 carbon atoms, n is an integer from 0 to 4,   M is lower alkenyl, lower alkynyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl, fused arylcycloalkyl, phenyl, lower alkylphenyl, phenyl-lower alkyl, hydroxyphenyl, methylenedioxyphenyl, bicycloalkyl-lower alkyl, lower alkylthio-lower alkyl, lower alkoxy-lower alkyl, halophenyl or, lower alkylthiophenyl, wherein the lower alkyl, lower alkenyl and lower alkynyl groups contain up to 6 carbon atoms and the cycloalkyl, cycloalkyl lower alkyl, bicycloalkyl, and fused aryl-cycloalkylkyl groups contain from 3 to 16 carbon atoms,   Y is hydroxy, lower alkoxy having 1 to 6 carbon atoms or amino,   R 7  is hydrogen, lower alkanoyl, benzoyl, ZS or ##STR14##  wherein the lower alkanoyl contains up to 6 carbon atoms Z is hydrogen, lower alkyl, hydroxy-lower alkyl, amino-lower alkyl, or a radical of the formula ##STR15##  wherein R 1 , R 2 , R 3 , R 4 , R 6 , n, M and Y are as defined above, and where Y is hydroxy, their non-toxic, pharmaceutically acceptable alkali metal, alkaline earth metal, and amine salts.   
     
     
       2. A compound according to claim 1 where R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are hydrogen or lower alkyl. 
     
     
       3. A compound according to claim 2 wherein n is 1. 
     
     
       4. A compound according to claim 3 wherein Y is hydroxy. 
     
     
       5. A compound according to claim 4 wherein R 1 , R 3 , R 4 , R 5  and R 6  are hydrogen and R 2  is lower alkyl. 
     
     
       6. A compound according to claim 5 wherein R 2  is methyl. 
     
     
       7. A compound according to claim 6 wherein R 7  is hydrogen. 
     
     
       8. A compound according to claim 6 wherein R 7  is lower alkanoyl. 
     
     
       9. A compound according to claim 8 wherein R 7  is acetyl. 
     
     
       10. A compound according to claim 7 wherein M is cyclopropyl. 
     
     
       11. A compound according to claim 7 wherein M is cyclopentyl. 
     
     
       12. A compound according to claim 9 wherein M is cyclopentyl. 
     
     
       13. A compound according to claim 7 wherein M is exo-norbornyl. 
     
     
       14. A compound according to claim 9 wherein M is exo-norbornyl. 
     
     
       15. A compound according to claim 7 wherein M is cyclobutyl. 
     
     
       16. A compound according to claim 7 wherein M is cycloheptyl. 
     
     
       17. A method of reducing the blood pressure in mammals having hypertension which comprises administering an effective amount of a compound of claim 1. 
     
     
       18. A compound according to claim 7 wherein M is 2-indanyl.